14 research outputs found

    2D nanostructures: Potential in diagnosis and treatment of Alzheimer's disease

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    Two-dimensional (2D) nanomaterials have garnered enormous attention seemingly due to their unusual architecture and properties. Graphene and graphene oxide based 2D nanomaterials remained the most sought after for several years but the quest to design superior 2D nanomaterials which can find wider application gave rise to development of non-graphene 2D materials as well. Consequently, in addition to graphene based 2D nanomaterials, 2D nanostructures designed using macromolecules (such as DNAs, proteins, peptides and peptoids), transition metal dichalcogenides, transition-metal carbides and/or nitrides (MXene), black phosphorous, chitosan, hexagonal boron nitrides, and graphitic carbon nitride, and covalent organic frameworks have been developed. Interestingly, these 2D nanomaterials have found applications in diagnosis and treatment of various diseases including Alzheimer’s disease (AD). Although AD is one of the most debilitating neurodegenerative conditions across the globe; unfortunately, there remains a paucity of effective diagnostic and/or therapeutic intervention for it till date. In this scenario, nanomaterial-based biosensors, or therapeutics especially 2D nanostructures are emerging to be promising in this regard. This review summarizes the diagnostic and therapeutic platforms developed for AD using 2D nanostructures. Collectively, it is worth mentioning that these 2D nanomaterials would seemingly provide an alternative and intriguing platform for biomedical interventions

    Illuminating the Petite Picture of T Cell Memory Responses to Listeria monocytogenes

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    The ease to culture, moderately less safety constraints in handling, and above all, hurdle free induction of an anticipated infection in mouse rendered Listeria monocytogenes the rank of a model organism for studying a variety of host immune responses. Listeria monocytogenes being an intracellular pathogen evokes potent CD8 T cell response during which CD8 T cells pass through a massive expansion phase. This is generally followed by contraction phase wherein majority of activated cells undergo apoptosis leaving behind a population of memory CD8 T cells that has potential to confer enhanced protection upon reencounter with the same pathogen. Functional attributes of various cytokines, transcription factors, receptors, adaptors, and effectors pertaining to the generation of robust memory T cell response have begun to be unravelled for better understanding of memory and opening avenues to create superior vaccine strategies. This review is an attempt to unveil related discoveries along with updating recent advances on this issue

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    Tissue specific heterogeneity in effector immune cell response

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    Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct ‘homing codes’ (adhesion molecules and chemokine receptors) during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A) and sunlight (vitamin D3) prime dendritic cells, imprinting them to play centrestage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues alongwith giving an overview of tissue tropism in B cells

    Plant based food bioactives: A boon or bane for neurological disorders

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    Neurological disorders are the foremost occurring diseases across the globe resulting in progressive dysfunction, loss of neuronal structure ultimately cell death. Therefore, attention has been drawn toward the natural resources for the search of neuroprotective agents. Plant-based food bioactives have emerged as potential neuroprotective agents for the treatment of neurodegenerative disorders. This comprehensive review primarily focuses on various plant food bioactive, mechanisms, therapeutic targets, in vitro and in vivo studies in the treatment of neurological disorders to explore whether they are boon or bane for neurological disorders. In addition, the clinical perspective of plant food bioactives in neurological disorders are also highlighted. Scientific evidences point toward the enormous therapeutic efficacy of plant food bioactives in the prevention or treatment of neurological disorders. Nevertheless, identification of food bioactive components accountable for the neuroprotective effects, mechanism, clinical trials, and consolidation of information flow are warranted. Plant food bioactives primarily act by mediating through various pathways including oxidative stress, neuroinflammation, apoptosis, excitotoxicity, specific proteins, mitochondrial dysfunction, and reversing neurodegeneration and can be used for the prevention and therapy of neurodegenerative disorders. In conclusion, the plant based food bioactives are boon for neurological disorders

    Pharmacological Inhibition of PTEN Rescues Dopaminergic Neurons by Attenuating Apoptotic and Neuroinflammatory Signaling Events

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    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta resulting in an irreversible and a debilitating motor dysfunction. Though both genetic and idiopathic factors are implicated in the disease etiology, idiopathic PD comprise the majority of clinical cases and is caused by exposure to environmental toxicants and oxidative stress. Fyn kinase activation has been identified as an early molecular signaling event that primes neuroinflammatory and neurodegenerative events associated with dopaminergic cell death. However, the upstream regulator of Fyn activation remains unidentified. We investigated whether the lipid and tyrosine phosphatase PTEN (Phosphatase and Tensin homolog deleted on chromosome 10) could be the upstream regulator of Fyn activation in PD models as PTEN has been previously reported to contribute to Parkinsonian pathology. Our findings, using bioluminescence resonance energy transfer (BRET) and immunoblotting, indicate for the first time that PTEN is a critical early stress sensor in response to oxidative stress and neurotoxicants in in vitro models of PD. Pharmacological attenuation of PTEN activity rescues dopaminergic neurons from neurotoxicant-induced cytotoxicity by modulating Fyn kinase activation. Our findings also identify PTEN’s novel roles in contributing to mitochondrial dysfunction which contribute to neurodegenerative processes. Interestingly, we found that PTEN positively regulates interleukin-1β (IL-1β) and the transcription of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Taken together, we have identified PTEN as a disease course altering pharmacological target that may be further validated for the development of novel therapeutic strategies targeting PD.</p

    Anti-Apoptosis and Anti-Fibrosis Effects of Eriobotrya Japonica in Spontaneously Hypertensive Rat Hearts

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    Myocardial apoptosis and fibrosis represent important contributing factors for development of hypertension-induced heart failure. The present study aims to investigate the potential effects of Eriobotrya japonica leaf extract (EJLE) against hypertension-induced cardiac apoptosis and fibrosis in spontaneously hypertensive rats (SHRs). Twelve-week-old male rats were randomly divided into four different groups; control Wistar Kyoto (WKY) rats, hypertensive SHR rats, SHR rats treated with a low dose (100 mg/kg body weight) of EJLE and SHR rats treated with a high dose (300 mg/kg body weight) of EJLE. Animals were acclimatized for 4 weeks and thereafter were gastric fed for 8 weeks with two doses of EJLE per week. The rats were then euthanized following cardiac functional analysis by echocardiography. The cardiac tissue sections were examined by Terminal Deoxynucleotidyl Transferase-Mediated Deoxyuridine Triphosphate (dUTP) Nick End-Labeling (TUNEL) assay, histological staining and Western blotting to assess the cardio-protective effects of EJ in SHR animals. Echocardiographic measurements provided convincing evidence to support the ability of EJ to ameliorate crucial cardiac functional characteristics. Furthermore, our results reveal that supplementation of EJLE effectively attenuated cardiac apoptosis and fibrosis and also enhanced cell survival in hypertensive SHR hearts. Thus, the present study concludes that EJLE potentially provides cardio-protective effects against hypertension-induced cardiac apoptosis and fibrosis in SHR animals

    Multifaceted Pharmacological Potentials of Curcumin, Genistein, and Tanshinone IIA through Proteomic Approaches: An In-Depth Review

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    Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future

    Multifaceted Pharmacological Potentials of Curcumin, Genistein, and Tanshinone IIA through Proteomic Approaches: An In-Depth Review

    Get PDF
    Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future
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